Gut microbiota and short-chain fatty acid alterations in cachectic cancer patients
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Ubachs J, Ziemons J, Soons Z, Aarnoutse R, van Dijk DPJ, Penders J, van Helvoort A, Smidt ML, Kruitwagen RFPM, Baade-Corpelijn L, Olde Damink SWM, Rensen SS
Journal
Journal of cachexia, sarcopenia and muscle
Year
2021
Keywords:
Breast cancer, Cachexia, Inflammation, Lung cancer, Pancreatic cancer, Weight loss
BACKGROUND: Cancer cachexia is characterized by a negative energy balance, muscle and adipose tissue wasting, insulin resistance, and systemic inflammation. Because of its strong negative impact on prognosis and its multifactorial nature that is still not fully understood, cachexia remains an important challenge in the field of cancer treatment. Recent animal studies indicate that the gut microbiota is involved in the pathogenesis and manifestation of cancer cachexia, but human data are lacking. The present study investigates gut microbiota composition, short-chain fatty acids (SCFA), and inflammatory parameters in human cancer cachexia. METHODS: Faecal samples were prospectively collected in patients (N = 107) with pancreatic cancer, lung cancer, breast cancer, or ovarian cancer. Household partners (N = 76) of the patients were included as healthy controls with similar diet and environmental conditions. Patients were classified as cachectic if they lost >5% body weight in the last 6 months. Gut microbiota composition was analysed by sequencing of the 16S rRNA V4 gene region. Faecal SCFA levels were quantified by gas chromatography. Faecal calprotectin was assessed with enzyme-linked immunosorbent assay. Serum C-reactive protein and leucocyte counts were retrieved from medical records. RESULTS: Cachexia prevalence was highest in pancreatic cancer (66.7%), followed by ovarian cancer (25%), lung cancer (20.8%), and breast cancer (17.3%). Microbial α-diversity was not significantly different between cachectic cancer patients (N = 33), non-cachectic cancer patients (N = 74), or healthy controls (N = 76) (species richness P = 0.31; Shannon effective index P = 0.46). Community structure (β-diversity) tended to differ between these groups (P = 0.053), although overall differences were subtle and no clear clustering of samples was observed. Proteobacteria (P < 0.001), an unknown genus from the Enterobacteriaceae family (P < 0.01), and Veillonella (P < 0.001) were more abundant among cachectic cancer patients. Megamonas (P < 0.05) and Peptococcus (P < 0.001) also showed differential abundance. Faecal levels of all SCFA tended to be lower in cachectic cancer patients, but only acetate concentrations were significantly reduced (P < 0.05). Faecal calprotectin levels were positively correlated with the abundance of Peptococcus, unknown Enterobacteriaceae, and Veillonella. We also identified several correlations and interactions between clinical and microbial parameters. CONCLUSIONS: This clinical study provided the first insights into the alterations of gut microbiota composition and SCFA levels that occur in cachectic cancer patients and how they are related to inflammatory parameters. These results pave the way for further research examining the role of the gut microbiota in cancer cachexia and its potential use as therapeutic target.
Experiment 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Subjects
- Location of subjects
- Netherlands
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Cancer CA,cancer,cell type cancer,malignancy,malignant Growth,malignant neoplasm,malignant neoplasm (disease),malignant neoplastic disease,malignant tumor,MT,neoplasm (disease), malignant,neoplasm, malignant,organ system cancer,primary cancer,Cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy Controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cachectic Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are cancer patients who lost >5% body weight in the last 6 months.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 76
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 Months
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- Wald Test
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure 2B& 3
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: increased abundance in Cachectic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonadota | ||
| Veillonella | ||
| unclassified Enterobacteriaceae |
Revision editor(s): Mautin
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure 2B &3
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: decreased abundance in Cachectic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Peptococcus |
Revision editor(s): Mautin
Experiment 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Cachectic Cancer
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cachetic Cancer
- Group 0 sample size Number of subjects in the control (unexposed) group
- 74
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure 2B,3
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: increased abundance in Cachetic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonadota | ||
| Veillonella | ||
| unclassified Enterobacteriaceae |
Revision editor(s): Mautin
Signature 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure 2B,3
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: decreased abundance in Cachetic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Megamonas | ||
| Peptococcus |
Revision editor(s): Mautin
Experiment 3
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Pancreatic carcinoma cancer of pancreas,cancer of the pancreas,carcinoma of exocrine pancreas,carcinoma of pancreas,carcinoma of the pancreas,exocrine cancer,exocrine pancreas carcinoma,exocrine pancreatic carcinoma,pancreas cancer,pancreas carcinoma,pancreatic cancer,pancreatic cancer (not islets),pancreatic carcinoma,pancreatic carcinoma, familial,Pancreatic carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy Controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cachectic Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are Pancreatic cancer patients who lost >5% body weight in the last 6 months analyzed for pancreatic Cancer
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure S3A
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: increased abundance in Cachectic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus | ||
| Lactobacillus | ||
| Veillonella | ||
| unclassified Enterobacteriaceae |
Revision editor(s): Mautin
Experiment 4
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-Cachectic Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are Pancreatic cancer patients who did not lost >5% body weight in the last 6 months.
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure S3A
Description: Distinct gut microbiota composition in Non-cachectic cancer patients
Abundance in Group 1: increased abundance in Non-Cachectic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus |
Revision editor(s): Mautin
Experiment 5
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Lung cancer alveolar cell carcinoma,cancer of lung,lung cancer,lung cancer, protection against,lung neoplasm,malignant lung neoplasm,malignant lung tumor,malignant neoplasm of lung,malignant neoplasm of the lung,malignant tumor of lung,malignant tumor of the lung,Nonsmall cell lung cancer,Lung cancer
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cachectic Cancer
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are Lung Cancer patients who lost >5% body weight in the last 6 months.
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure S3B
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: increased abundance in Cachectic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Enterococcus |
Revision editor(s): Mautin
Experiment 6
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Cachectic Cancer
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-13
Source: Figure S3B
Description: Distinct gut microbiota composition in cachectic cancer patients
Abundance in Group 1: increased abundance in Cachectic Cancer
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus |
Revision editor(s): Mautin
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